Genotype/phenotype correlations in 538 congenital adrenal hyperplasia patients from Germany and Austria: discordances in milder genotypes and in screened versus prescreening patients

Journal article


Publication Details

Author(s): Riedl S, Roehl FW, Bonfig W, Braemswig J, Richter-Unruh A, Fricke-Otto S, Bettendorf M, Riepe F, Kriegshaeuser G, Schoenau E, Even G, Hauffa B, Dörr HG, Holl RW, Mohnike K
Journal: Endocrine Connections
Publication year: 2019
Volume: 8
Journal issue: 2
Pages range: 86-94
ISSN: 2049-3614


Abstract

Congenital adrenal hyperplasia (CAH) due to CYP21A2 gene mutations is associated with a variety of clinical phenotypes (salt wasting, SW; simple virilizing, SV; nonclassical, NC) depending on residual 21-hydroxylase activity. Phenotypes and genotypes correlate well in 80-90% of cases. We set out to test the predictive value of CAH phenotype assignment based on genotype classification in a large multicenter cohort. A retrospective evaluation of genetic data from 538 CAH patients (195 screened) collected from 28 tertiary centers as part of a German quality control program was performed. Genotypes were classified according to residual 21-hydroxylase activity (null, A, B, C) and assigned clinical phenotypes correlated with predicted phenotypes, including analysis of Prader stages. Ultimately, concordance of genotypes with clinical phenotypes was compared in patients diagnosed before or after the introduction of nationwide CAH-newborn screening. Severe genotypes (null and A) correlated well with the expected phenotype (SW in 97 and 91%, respectively), whereas less severe genotypes (B and C) correlated poorly (SV in 45% and NC in 57%, respectively). This was underlined by a high degree of virilization in girls with C genotypes (Prader stage >1 in 28%). SW was diagnosed in 90% of screening-positive babies with classical CAH compared with 74% of prescreening patients. In our CAH series, assigned phenotypes were more severe than expected in milder genotypes and in screened vs prescreening patients. Diagnostic discrimination between phenotypes based on genotypes may prove overcome due to the overlap in their clinical presentations.


FAU Authors / FAU Editors

Dörr, Helmuth-Günther Prof. Dr.
Professur für Kinderheilkunde mit dem Schwerpunkt Kinder-Endokrinologie und Diabetologie (Stiftungsprofessur)


External institutions with authors

HELIOS Kliniken
Klinikum Wels-Grieskirchen
Landeskrankenhaus Steyr (LKH Steyr)
Medizinische Universität Wien
Otto-von-Guericke-Universität Magdeburg
Ruprecht-Karls-Universität Heidelberg
Universität Duisburg-Essen (UDE)
Universität Köln
Universität Ulm
Westfälische Wilhelms-Universität (WWU) Münster


How to cite

APA:
Riedl, S., Roehl, F.-W., Bonfig, W., Braemswig, J., Richter-Unruh, A., Fricke-Otto, S.,... Mohnike, K. (2019). Genotype/phenotype correlations in 538 congenital adrenal hyperplasia patients from Germany and Austria: discordances in milder genotypes and in screened versus prescreening patients. Endocrine Connections, 8(2), 86-94. https://dx.doi.org/10.1530/EC-18-0281

MLA:
Riedl, Stefan, et al. "Genotype/phenotype correlations in 538 congenital adrenal hyperplasia patients from Germany and Austria: discordances in milder genotypes and in screened versus prescreening patients." Endocrine Connections 8.2 (2019): 86-94.

BibTeX: 

Last updated on 2019-21-03 at 22:08